The goal of this proposal is to apply Terahertz Spectroscopy (THz) to biological samples. THz radiation has a fundamental period around 1ps that allows the study and control of various systems such as small molecule rotation, highly excited atomic Rydberg states that orbit at THz frequencies, and the collisions of gas phase molecules at room temperature. Of importance to biological researchers is that the collective modes of proteins vibrate at THz frequencies, as do frustrated rotations and collective modes of polar solvents, especially water. This latter property also allows the water content to be the marker for bioimaging. The use of femtosecond lasers and the development of photoconductive antennae as transmitters and receivers have lowered the cost down to the average research lab. The Miami University THz group is part of a larger team consisting of Wright-Patterson Air Force Base, Cincinnati's Children's Hospital, and Picometrix who are researching the utility of THz in a variety of applications. The importance of developing THz has recently been supported by the DOE-NSF-NIH 2004 report "Opportunities in THz Science". There are three specific aims; 1) acquisition of THz spectral information on biomolecules; 2) using THz for bioimaging; and 3) understanding the nature and role of water in nanomaterials and biological systems. Although the proposal work in this proposal is more fundamental THz investigations, the long term goals are label-free sensors based on complementary DMA hybridization and of near-field probes used in label-free measurements of protein-protein interactions occurring in living cells. This work will support a longer term goal of interrogating non-equilibrium systems using pump/probe asynchronous sampling that would stimulate the biological samples and use THz to monitor any structural/electronic changes. This use of THz within the fields of skin research, medical diagnostics, and development of improved therapeutic modalities (e.g., epidermal barrier development, noninvasive skin imaging, transdermal drug delivery, and drug efficacy). Work on THz spectroscopy of the air/water, water/solid, and water/membrane biointerfaces and the longer- term investigations into the interactions of the protein surface with water. [unreadable] [unreadable] [unreadable]